Neoductular progenitor cells regenerate hepatocytes in severely damaged liver: a comparative ultrastructural study

Abstract

In severely injured liver, stem cells give rise to progeny that tend to replace lost hepatocytes. Neoductular reaction appears as an inherent stage of liver reconstruction following severe damage caused by different pathological mechanisms. Few ultrastructural types of progenitor cells have been described, and some molecular phenotypes of progenitor stages have been characterized, but the details of the differentiation process are largely unknown. We prepared for light and electron microscopy examination human liver from biopsies of patients with chronic active hepatitis, and rat liver with allyl alcohol‐induced periportal necrosis. We found that progenitor neoductular cells acquire the hepatocytic polarity pattern during a multi‐step process apparently involving cell migration and dissolution of neoductular basement membrane. An intermediate stage with “mixed” ductular and hepatocytic polarity was described.

Neuroregulation of the neuroendocrine compartment of the liver

“…Oval cells express phenotypic markers of both (immature) hepatocytes (such as α‐fetoprotein) and bile duct cells (such as bile duct‐type cytokeratins) (Germain et al, 1985; Hixson and Allison, 1985; Dunsford et al, 1989; Dabeva et al, 1993). They constitute a heterogeneous cell population (Germain et al, 1985; Hixson and Allison, 1985; Dunsford and Sell, 1989; Dabeva and Shafritz, 1993; Dabeva et al, 1993; Mandache et al, 2002), but at least a subset of oval cells is pluripotent and has the capacity to differentiate toward hepatocytes, bile ductular cells, and intestinal epithelium and can give rise to hepatocellular carcinoma and cholangiocellular carcinoma (Grisham, 1980; Evarts, 1987, 1996; Tsao, 1987; Sell, 1990; Yasui, 1997; Alison, 2001). A new light was shed on the liver progenitor cell field with studies suggesting that bone marrow‐derived stem cells can give rise to hepatocytes, oval cells, and bile duct cells (Petersen et al, 1999; Alison et al, 2000; Theise et al, 2000a; Korbling et al, 2002).…”

“…Intermediate hepatobiliary cells are polygonal cells with a size and phenotype intermediate between progenitor cells and hepatocytes (Roskams et al, 1991, 1998; Demetris et al, 1996; Theise et al, 1999). Different subtypes of progenitor cells have also been recognized by electron microscopy: the most immature progenitor cell type besides cells already featuring some biliary or hepatocytic features (De Vos and Desmet, 1992; Xiao et al, 1999, 2003; Mandache et al, 2002). This spectrum of cells ranging from the most immature phenotype to ductules and intermediate hepatocytes forms a cell compartment with a specific phenotype and is often referred to as the progenitor cell compartment.…”

Progenitor Cells in Diseased Human Liver

“…37,64 Different subtypes of progenitor cells have also been recognized by electron microscopy, including the most immature progenitor cells and cells that feature some biliary or hepatocytic properties. 19,46,56,65 The most undifferentiated cell is connected by junctional complexes to adjacent cells and contains bundles of tonofilaments. A second cell type shows some biliary features, including lateral interdigitations of the plasmalemma, apical microvilli, basal pinocytotic vacuoles, and a well-developed basement membrane.…”

“…These cells were called oval cells because of their shape, 2,3 and this name is widely used for hepatic progenitor cells in animal liver. An extensive tute a heterogeneous cell population, 13,14,[16][17][18][19] but at least a subset of oval cells is pluripotent and has the capacity to differentiate toward hepatocytes, bile ductular cells, and intestinal epithelium and can give rise to hepatocellular carcinoma and cholangiocellular carcinoma. 6,9,[20][21][22][23][24][25][26] A new light was shed on the liver progenitor cell field with studies that suggested that bone marrow-derived stem cells can give rise to hepatocytes, oval cells, and bile duct cells.…”

Progenitor cell involvement in cirrhotic human liver diseases: from controversy to consensus

“…Intermediate hepatocytes are polygonal cells with a size and phenotype intermediate between progenitor cells and hepatocytes [30,31,55,56]. Different subtypes of progenitor cells have also been recognized by electron microscopy: the most immature progenitor cell type besides cells already featuring some biliary or hepatocytic features [20,39,57,58]. This spectrum of cells ranging from the most immature phenotype to ductules and intermediate hepatocytes, forms a cell compartment with a specific phenotype, and is often referred to as the 'progenitor cell compartment'.…”